Macromolecular crystallography plays a central role in biomedical research. At the University of Massachusetts Medical School, crystallographic analysis supports the research of more than 10 investigators. This instrumentation is used in the research that is supported by 13 NIH grants and trains more than 25 graduate students. Our current instrumentation can no longer be depended upon. Even when properly functioning the current instrumentation is incapable of serving the cutting-edge research programs many of the investigators require. A Shared Instrumentation Grant will allow us to purchase a new diffraction system and numerous programs will no longer be limited by an outdated machine. Specifically, we are requesting funds for a Rigaku HighFlux HomeLab x-ray diffraction system with an R-AXIS IV++ image plate detector. For many of our projects this new system will permit data acquisition that is sufficient to answer essential questions in macromolecular structure and drug design. For other research programs, the new system will allow local screening of crystals making synchrotron trips much more efficient. Thus the acquisition of this state-of-the-art crystallographic system will propel our research programs far beyond what we can currently achieve. PUBLIC HEALTH RELEVANCE: Modern medicine requires an understanding of the detailed structures of biological molecules. In this proposal we request funds for an x-ray diffraction system, which will allow us to determine such key biological structures in atomic detail. These details will be used in drug design and in understanding the molecular mechanisms of many human diseases.